ADAPTIVE-CHANGES OF HEPATIC BILE-SALT TRANSPORT IN A MODEL OF REVERSIBLE INTERRUPTION OF THE ENTEROHEPATIC CIRCULATION IN THE RAT

The reversibility and time course of the adaptive changes in hepatic bile salt transport related to modifications of the bile salt enterohepatic circulation and bile salt pool size have not been previously studied. For this reason a model of reversible interruption of entero-hepatic circulation was characterized in unrestrained rats, which allowed the study of changes in hepatic bile salt transport following bile salt pool depletion and subsequent restoration by either the de novo synthesis of bile acids or i.v. administration of exogenous taurocholate. Rats subjected to biliary drainage for 24 h through a transduodenal common bile duct cannula, followed by removal of the cannula and restoration of the enterohepatic circulation were studied at 24, 48 and 72 h. Neither light and electron microscopy examination nor plasma biochemical parameters showed evidence of necrosis, fibrosis, cholestasis or inflammatory changes. Maximum taurocholate secretory rate decreased to 50% following 24-h bile salt depletion. After restoration of the enterohepatic circulation maximum taurocholate secretory rate progressively increased to normal values at 72 h, following the normalization of the bile salt pool size, which had a similar composition compared with controls. The same effect was obtained when the native bile salt pool was substituted with exogenous taurocholate. Thus, adaptive down-regulation of hepatic bile salt transport capacity is a reversible process, related to restoration of entero-hepatic circulation and normalization of bile salt pool size.